La eritropoyetina humana recombinante reduce la disfunción sensoriomotora y el deterioro cognitivo en ratas con enfermedad renal crónica / Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease

INTRODUCCIÓN: La enfermedad renal crónica (ERC) puede provocar anemia e inducir afectaciones neurológicas. La eritropoyetina humana recombinante (rHuEPO) se utiliza en el tratamiento de la anemia en la ERC. Sin embargo, existe poca evidencia de los efectos de la rHuEPO sobre la conducta y las funciones cognitivas en la ERC. El objetivo de este estudio fue evaluar el efecto del tratamiento con rHuEPO sobre las funciones sensoriomotoras y cognitivas en un modelo de ERC. MÉTODOS: Ratas macho de la cepa Wistar fueron asignadas a 4 grupos: control y ERC, con y sin tratamiento con rHuEPO (1.050 UI/kg de peso, una vez por semana durante 4 semanas). Las pruebas conductuales de laberinto acuático de Morris, campo abierto y cinta adhesiva se realizaron de manera simultánea a la inducción del daño renal y el tratamiento. Mientras que la determinación de marcadores de función renal y anemia se realizaron al término del estudio. RESULTADOS: El tratamiento con rHuEPO redujo el daño en el riñón y corrigió la anemia en las ratas con ERC. En las pruebas conductuales, el tratamiento con rHuEPO redujo la disfunción sensoriomotora observada en los animales con ERC. Por otra parte, en los animales con ERC y tratamiento con rHuEPO resolvieron el laberinto en menor tiempo en comparación a los grupos control. CONCLUSIONES: El tratamiento con rHuEPO reduce el daño en el riñón, corrige la anemia y reduce la disfunción sensoriomotora y cognitiva en los animales con ERC

INTRODUCTION: Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. METHODS: Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. RESULTS: Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. CONCLUSIONS: rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD

Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease. / La eritropoyetina humana recombinante reduce la disfunción sensoriomotora y el deterioro cognitivo en ratas con enfermedad renal crónica.

INTRODUCTION: Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. METHODS: Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. RESULTS: Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. CONCLUSIONS: rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD.

Spruce xylan/HEMA-SBA15 hybrid hydrogels as a potential scaffold for fibroblast growth and attachment.

A hybrid hydrogel (GHC-SBA15) based on spruce xylan (HC), 2-hydroxyethyl methacrylate (HEMA), and mesoporous silica (SBA15) was prepared with the intended use of fibroblast attachment and growth. Xylan was functionalized with acryloyl chloride to introduce vinyl groups and was crosslinked by radical polymerization with HEMA in presence of SBA15. Infrared spectroscopy and nuclear magnetic resonance confirmed the copolymerization of HEMA with xylan. Up to 20 wt.% addition, SBA15 was homogenously incorporated in the structured hydrogel network as observed by SEM. Moreover, nitrogen adsorption-desorption, small angle X-ray scattering and transmission electron microscopy indicated that the mesoporous SBA15 framework was maintained and that the hybrid hydrogel was a physical mixture of SBA15 with the copolymer HC/HEMA. Rheological analysis revealed that addition of 20% w/w SBA15 into hydrogel enhanced significantly the mechanical properties. In addition, we demonstrate that fibroblast L929 cells grew and spread on GHC-SBA15. Cell viability was within the expected range.

Colágenas Recombinantes para Andamios de Ingeniería de Tejidos / Recombinant Collagens for Tissue Engineering Scaffolds

Resumen: Las colágenas son cada día más atractivas en la fabricación de andamios para Ingeniería de Tejidos, por su biocompatibilidad, manejo y capacidad de producirlas industrialmente. El objetivo del presente artículo fue presentar un análisis sobre el avance en la investigación, el desarrollo y producción de colágenas recombinantes de humano, los sistemas de producción y sus usos en Ingeniería de Tejidos. Se realizó una revisión de la literatura científica internacional arbitrada en bases de datos como Scopus, PubMed y Google Académico y se empleó aquella relevante a nuestro objetivo. Se encontró que el desarrollo de colágenas recombinantes de humano muestra un avance significativo y en la actualidad los sistemas de expresión, como bacterias y plantas, presentan ventajas sobre la calidad de la estructura y la biocompatibilidad, aunque con rendimientos todavía bajos. Mientras que existe escasa información sobre sus aplicaciones en Ingeniería de Tejidos, principalmente cartílago y hueso, en modelos animales y estudios clínicos. En las fuentes de información no se incluyeron patentes, por lo que nuestros hallazgos están limitados a publicaciones científicas. El presente trabajo, presenta los avances más recientes sobre la ingeniería de colágenas recombinantes y sus aplicaciones biomédicas en fabricación de tejidos con potencial uso clínico. Por lo que su factibilidad en la medicina regenerativa es prometedor y se requiere mayor investigación que permita su aplicación en un futuro cercano.

Abstract: Due to its biocompatibility, handling and industrial production capacity, collagens have been increasingly attractive in the manufacture of scaffolds for Tissue Engineering. The aim of the present work was to present an analysis on the progress in research, development and production of human recombinant collagens, expression systems and their uses in Tissue Engineering. A review of the international scientific peer-reviewed literature in databases such as Scopus, PubMed and Google Scholar was done and that relevant to our objective was employed. The development of human recombinant collagens was found to be significant, and currently the expression systems, like bacteria and plants, show advantages over structure quality and biocompatibility, albeit with still restricted yields. However, there is narrow information about its applications in Tissue Engineering, mostly studied for cartilage and bone, in animal models and clinical studies. We did not include patents in the study, thus our findings are limited to scholar data. The present work presents the most recent advances in the engineering of recombinant collagens and their biomedical applications in the manufacture of tissues with potential clinical applications. The potential of recombinant collagens in regenerative medicine is promising and more research is needed that might allow a broad application in the near future.

Development of the endocrine pancreas and novel strategies for beta-cell mass restoration and diabetes therapy

Diabetes mellitus represents a serious public health problem owing to its global prevalence in the last decade. The causes of this metabolic disease include dysfunction and/or insufficient number of β cells. Existing diabetes mellitus treatments do not reverse or control the disease. Therefore, β-cell mass restoration might be a promising treatment. Several restoration approaches have been developed: inducing the proliferation of remaining insulin-producing cells, de novo islet formation from pancreatic progenitor cells (neogenesis), and converting non-β cells within the pancreas to β cells (transdifferentiation) are the most direct, simple, and least invasive ways to increase β-cell mass. However, their clinical significance is yet to be determined. Hypothetically, β cells or islet transplantation methods might be curative strategies for diabetes mellitus; however, the scarcity of donors limits the clinical application of these approaches. Thus, alternative cell sources for β-cell replacement could include embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. However, most differentiated cells obtained using these techniques are functionally immature and show poor glucose-stimulated insulin secretion compared with native β cells. Currently, their clinical use is still hampered by ethical issues and the risk of tumor development post transplantation. In this review, we briefly summarize the current knowledge of mouse pancreas organogenesis, morphogenesis, and maturation, including the molecular mechanisms involved. We then discuss two possible approaches of β-cell mass restoration for diabetes mellitus therapy: β-cell regeneration and β-cell replacement. We critically analyze each strategy with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.

Development of the endocrine pancreas and novel strategies for ß-cell mass restoration and diabetes therapy.

Diabetes mellitus represents a serious public health problem owing to its global prevalence in the last decade. The causes of this metabolic disease include dysfunction and/or insufficient number of ß cells. Existing diabetes mellitus treatments do not reverse or control the disease. Therefore, ß-cell mass restoration might be a promising treatment. Several restoration approaches have been developed: inducing the proliferation of remaining insulin-producing cells, de novo islet formation from pancreatic progenitor cells (neogenesis), and converting non-ß cells within the pancreas to ß cells (transdifferentiation) are the most direct, simple, and least invasive ways to increase ß-cell mass. However, their clinical significance is yet to be determined. Hypothetically, ß cells or islet transplantation methods might be curative strategies for diabetes mellitus; however, the scarcity of donors limits the clinical application of these approaches. Thus, alternative cell sources for ß-cell replacement could include embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. However, most differentiated cells obtained using these techniques are functionally immature and show poor glucose-stimulated insulin secretion compared with native ß cells. Currently, their clinical use is still hampered by ethical issues and the risk of tumor development post transplantation. In this review, we briefly summarize the current knowledge of mouse pancreas organogenesis, morphogenesis, and maturation, including the molecular mechanisms involved. We then discuss two possible approaches of ß-cell mass restoration for diabetes mellitus therapy: ß-cell regeneration and ß-cell replacement. We critically analyze each strategy with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.

Impaired activation of Stat1 and c-Jun as a possible defect in macrophages of patients with active tuberculosis.

Studies of patients with active tuberculosis (TB) and infected healthy individuals have shown that interferon (IFN)-gamma is present in sites of Mycobacterium tuberculosis infection in comparable levels. This suggests that there is a deficiency in the macrophage response to IFN-gamma in TB patients. We used recombinant human IFN-gamma to stimulate adherent monocyte-derived macrophages from three groups of people: patients with active tuberculosis (TBP), their healthy household contacts (HHC) and healthy uninfected controls from the community (CC). We then evaluated the ability of the macrophages to inhibit the growth of M. tuberculosis H37Rv as well as their cytokine profile at early in infection (48 h). After IFN-gamma treatment, macrophages of healthy individuals (HHC and CC) controlled M. tuberculosis growth and produced mainly nitric oxide (NO) and interleukin (IL)-12p70, whereas TBP macrophages did not kill M. tuberculosis. Additionally, TBP macrophages produced low levels of NO and IL-12p70 and high levels of tumour necrosis factor (TNF)-alpha and IL-10. Transforming growth factor (TGF)-beta levels were similar among all three groups. M. tuberculosis infection had little effect on the cytokine response after IFN-gamma stimulus, but infection alone induced more IL-10 and TGF-beta in TBP macrophages. There were no differences in Stat1 nuclear translocation and DNA binding between the groups. However, the phosphorylated Stat1 and c-Jun (AP-1) in nuclear protein extracts was diminished in TBP macrophages compared to macrophages of healthy individuals. These results indicate an impairment of Stat1-dependent and Stat1-independent IFN-gamma signalling in macrophages of people with active tuberculosis, suggesting a different molecular regulation that could impact macrophage functionality and disease outcome.